7NEU

Inhibitor Complex with Thrombin Activatable Fibrinolysis Inhibitor (TAFIa)

7NEU の概要

• エントリーDOI: 10.2210/pdb7neu/pdb
• 分子名称: Carboxypeptidase B2, (1R,3S)-3-(4-ammoniobutyl)-1-(4-fluoro-2-(1-methyl-1H-imidazol-5-yl)benzyl)-1,4-azaphosphinan-1-ium-3-carboxylate 4,4-dioxide, ZINC ION, ... (8 entities in total)
• 機能のキーワード: inhibitor, complex, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 47031.81

構造登録者

Brown, D.G.,Schaffner, A.P.,Vuillard, L.M.,Gloanec, P.,Raimbauld, E. (登録日: 2021-02-04, 公開日: 2021-04-07, 最終更新日: 2024-11-06)

主引用文献

Schaffner, A.P.,Sansilvestri-Morel, P.,Despaux, N.,Ruano, E.,Persigand, T.,Rupin, A.,Mennecier, P.,Vallez, M.O.,Raimbaud, E.,Desos, P.,Gloanec, P.
Phosphinanes and Azaphosphinanes as Potent and Selective Inhibitors of Activated Thrombin-Activatable Fibrinolysis Inhibitor (TAFIa).
J.Med.Chem., 64:3897-3910, 2021

PubMed Abstract: Selective and potent inhibitors of activated thrombin activatable fibrinolysis inhibitor (TAFIa) have the potential to increase endogenous and therapeutic fibrinolysis and to behave like profibrinolytic agents without the risk of major hemorrhage, since they do not interfere either with platelet activation or with coagulation during blood hemostasis. Therefore, TAFIa inhibitors could be used in at-risk patients for the treatment, prevention, and secondary prevention of stroke, venous thrombosis, and pulmonary embolisms. In this paper, we describe the design, the structure-activity relationship (SAR), and the synthesis of novel, potent, and selective phosphinanes and azaphosphinanes as TAFIa inhibitors. Several highly active azaphosphinanes display attractive properties suitable for further efficacy studies in thrombosis models.

PubMed: 33764059
DOI: 10.1021/acs.jmedchem.0c02072

実験手法

X-RAY DIFFRACTION (2.8 Å)